Regulation of microtubule nucleation by Mto1/2 complex and the gamma-tubulin complex. (360G-Wellcome-094517_Z_10_Z)
Regulation of microtubule nucleation is important for spatiotemporal control of microtubule distribution in eukaryotic cells and for many aspects of cell division and differentiation. Nucleation from both the centrosome and non-centrosomal sites involves the gamma-tubulin complex, but regulation of the gamma-tubulin complex is not well-understood. We will investigate this using fission yeast as a model system. We discovered two proteins, Mto1 and Mto2, that form a complex (Mto1/2) that both l ocalizes the gamma-tubulin complex to multiple intracellular sites and activates the gamma-tubulin complex to make it a functional nucleator. We will determine the molecular mechanisms by which Mto1/2 regulates microtubule nucleation by the gamma-tubulin complex, using a combination of genetics, microscopy, biochemistry/proteomics, in vitro functional assays and structural analysis. As the localization of Mto1/2 dictates where cytoplasmic microtubule nucleation occurs, we will identify the p roteins and mechanisms targeting Mto1/2 to distinct sites in the cell. To understand how Mto1/2 activates the gamma-tubulin complex from a mechanistic perspective, we will study the complexes in vitro, using a variety of methods, including functional reconstitution with purified proteins, chemical cross-linking and mass-spectrometry, and single-particle electron microscopy. Finally, we will address how the organization and localization of Mto1/2 is regulated by the cell cycle.
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Grant Details
Amount Awarded | 1026911 |
Applicant Surname | Sawin |
Approval Committee | Molecules, Genes and Cells Funding Committee |
Award Date | 2011-03-09T00:00:00+00:00 |
Financial Year | 2010/11 |
Grant Programme: Title | Programme Grant |
Internal ID | 094517/Z/10/Z |
Lead Applicant | Prof Kenneth Sawin |
Partnership Value | 1026911 |
Planned Dates: End Date | 2018-04-10T00:00:00+00:00 |
Planned Dates: Start Date | 2012-04-11T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Scotland |